IMMUNOGENETIC AND PHARMACOCHEMICAL CHARACTERIZATION OF THE ABO SYSTEM GLYCOPROTEIN PROPERTIES AS CRITERIA OF INDIVIDUAL SENSITIVITY TO ANTITUMOR AGENT BORTEZOMIB IN THE PLASMA CELL MYELOMA PATIENTS. / IMUNOGENETYChNYY̆ TA FARMAKOKhIMIChNYY̆ ANALIZ VLASTYVOSTEY̆ GLIKOPROTEÏNIV SYSTEMY AVO IaK KRYTERIÏV INDYVIDUAL'NOÏ ChUTLYVOSTI ShchODO PROTYPUKhLYNNOGO PREPARATU BORTEZOMIBU U KhVORYKh NA PLAZMOKLITYNNU MIIeLOMU.

OBJECTIVE: Experimental study of the effect profile of bortezomib in the plasma cell myeloma (PCM) patients depend- ing on a specific phenotype carrier state and a pharmacochemical characteristics of ABO system glycoproteins. MATERIALS AND METHODS: The research was conducted on the 104 PCM patients, including the Chornobyl NPP acci- dent survivors (n = 49) and 65 study subjects in the comparison group. Immunogenetic criteria for positive response to the applied treatment protocols were issued according to the duration of remission, absence of infectious com- plications, and evidence of chronic renal failure as a disease complication. RESULTS: Possibility of glycoproteins A and B participation in the formation of human biological individuality at a level of protein-protein interaction with antineoplastic drug bortezomib, which is widely used in cancer management prac- tice, in particular in the PCM treatment is considered. The glycoprotein B was shown being a selective target for borte- zomib, slowing down the recognition and interaction of antigen B with monoclonal anti-B antibody, while the agglu- tination period lengthens at that by 66 %. Assumption that the formation of bortezomib complex with glycoprotein B provides a background for interaction with the key reaction of proteasome 26S inhibition, which to some extent con- tributes to the drug effect retardation was confirmed through the quantum-chemical calculations. Equilibrium is shift- ed toward the main reaction leading to a higher drug efficacy in patients with blood groups O (I) and A (II). CONCLUSIONS: Since the complexation occurs predominantly in alkaline medium the administration of drugs with alkaline reaction should be restricted for at least round the clock after administration of bortezomib according to its half-life in plasma in patients with B (III) blood group and chronic renal failure.

CLINICAL, HEMATOLOGICAL CHARACTERIZATION AND POLYMORPHISM OF ABO AND Rh BLOOD GROUP SYSTEMS IN PLASMA CELL MYELOMA PATIENTS. / KLINIKO-GEMATOLOGIChNA KhARAKTERYSTYKA TA POLIMORFIZM SYSTEM GRUP KROVI AVO TA Rh U KhVORYKh NA PLAZMOKLITYNNU MIIeLOMU.

Objective to study the peculiarities of clinical characteristics and polymorphism of ABO and Rh blood group systemsin relation to the natural history of plasma cell myeloma in the ChNPP accident survivors. MATERIALS AND METHODS: Peculiarities of the disease natural history were reviewed in the 111 plasma cell myeloma(PCM) patients receiving medical management at the Department of Radiation Oncohematology of the NRCRM dur-ing 2010-2017. Principal clinical and laboratory characteristics of PCM, namely the values/levels of LDH, ß2-mic-roglobulin, albumin, serum calcium, urea, creatinine and hemoglobin were assessed, taking into account the gender,radiation history (ChNPP accident clean-up workers, evacuees from areas of obligatory resettlement, inhabitants ofcontaminated territories, and the comparison group) and the PCM stage codenamed by Durie-Salmon et al. (1975)and the ISS (1985) classifications. Distribution of polymorphic variants on ABO and Rh blood systems was studiedin the 106 PCM patients. RESULTS: It was found that the level of ß2-micro-globulin and calcium was increased significantly in male (p = 0.02and p = 0.04, respectively), whereas serum urea content was elevated in female (p = 0.04) PCM patients featuring acompromised radiation anamnesis in comparison to non-irradiated patients. Some probable differences were foundfor urea level (F = 3.58, p = 0.05) and serum albumin (F = 4.00, p = 0.05) in the examined group of PCM patients.Probable (p < 0.05) incidence increase of the B phenotype was established as a predictor of complicated natural his-tory of PCM with abnormal genetic equilibrium resulted from the increased incidence of IB allele in chronic renal fail-ure (CRF) patients. Significant (p < 0.05) prolongation of the remission period upon a standard PCT application wasfound in PCM patients being the A phenotype carriers having a preserved gene and phenotypic equilibrium comparedwith carriers of O and B phenotypes. CONCLUSIONS: Clinical and hematological parameters are different in PCM patients survived after the ChNPP accidentand those with favorable radiation history. Distribution of polymorphic variants of ABO antigenic structures inpatients with complicated natural history of the disease is also different, that can be a background for predictingthe effectiveness of treatment. Further research is required in this field.